Surgical intervention, by its very nature, results in tissue damage that triggers the formation of fibrotic sear tissue as part of the normal wound healing response. Although inflammation and production of extracellular matrix components is necessary for normal wound healing, adhesions may also occur which can lead to significant clinical complications. Simple bioresorbable barriers made from hyaluronic acid, regenerated cellulose, or collagen have been shown to have some efficacy in preventing inter-tissue adhesions, but there are still a significant number of adhesions that occur using this strategy. Another strategy to eliminate post-surgical adhesions is to provide an adsorbable barrier between tissue planes which releases an agent which inhibits collagen production, the main protein component of scar tissue. For example, cis-4-hydroxyproline (cHyp) has been shown to be a potent inhibitor of synthesis of collagen, and thus has been considered as a potential antifibrotic agent. In the Phase I studies, cHyp was attached to a water soluble polymer (denoted as poly[PEG-Lys-cHyp]) consisting of low molecular weight PEG and Lys to reduce the toxicity and improve the efficacy of cHyp. The lysine component has a free carboxylic acid pendent group at each monomeric repeat unit which can be used to couple active agents such as cHyp.. The polymers were found to sustain release, reduce toxicity, and increase antifibrotic potency of attached cHyp in preliminary in vitro studies. Furthermore, a highly reliable, clinically-relevant animal model (rabbit) was developed during the Phase I studies. Adhesions were first created along the abdominal wall, cecum, and right uterine horn; the adhesions were confirmed, than lyzed, prior to application of the test compounds. An initial series of in vivo studies using adhesiolytes model showed that the sustained release cHyp provided a high degree of efficacy in a dose-dependent manner. The goal of these proposed Phase II studies is to further develop the compound formulation and to begin pre-clinical efficacy, toxicity, and safety studies. As in Phase I, any modification of the formulation and to begin pre-clinical efficacy, toxicity, toxicity, and safely studies. As in Phase I, any modification of the formulation of the formulation will be first tested using cell culture, followed by in vivo assays to determine the potential bioactivity of this compound. PROPOSED COMMERCIAL APPLICATION: A number of approaches have been pursued to limit the complication of post-surgical adhesions, such as the use of non-resorbable and resorbable barriers, and using active agents to inhibit or minimize adhesion formation. Despite the product development activity in this filed, there are currently only two products available for clinical use, with neither product reducing adhesions by more than 55%. An effective product would have a major impact on patient morbidity and health care economics.